Cancer is characterized by the increase in the number of abnormal, or neoplastic, cells derived from a normal tissue which proliferate to form a tumor mass, the invasion of adjacent tissues by these neoplastic tumor cells, and the generation of malignant cells which eventually spread via the blood or lymphatic system to regional lymph nodes and to distant sites via a process called metastasis. The identification of such tumor-associated cell surface antigen polypeptides has given rise to the ability to specifically target cancer cells for destruction via antibody-based therapies. In attempts to discover effective cellular targets for cancer therapy or detection, researchers have sought to identify polypeptides that are specifically overexpressed on the surface of a particular type of cancer cell as compared to on one or more normal non-cancerous cell(s). In other attempts to discover effective cellular targets for cancer therapy, researchers have sought to identify polypeptides that are produced and secreted by a particular type of cancer cell at an expression level that is higher than that produced and secreted by one or more normal non-cancerous cell(s). Despite the above identified advances in mammalian cancer therapy, there is a great need for additional diagnostic and therapeutic agents capable of detecting the presence of tumor in a mammal and for treating cancer, respectively.
Enolase was originally characterized as an enzyme involved in glycolytic metabolism catalyzing the conversion of 2-phosphoglycerate into phosphoenolpyruvate. In mammals there are three isoforms of enolase, called α-ENO1, β-ENO3 and γ-ENO2. The α-enolase is a major from of enolase present in the early stages of embryonic development, being expressed ubiquitously in various types of tissue, whereas γ-ENO2 and β-ENO3 are exclusively found in neuron and muscle cells (Antikainen et al., 2007, FEMS Immunol Med Microbiol 51, 526-534; Chang, et al., 2006, Clin Cancer Res 12, 5746-5754). The information regarding nucleic acid and amino acid sequences of α-enolase can be obtained from NCBI website. It was reported that α-enolase is a multifunctional protein which exhibits enzymatic, structural, and receptor functions (Chang, et al., 2006, Clin Cancer Res 12, 5746-5754; Lee et al., 2003, Arthritis Rheum 48, 2025-2035). In addition to its glycolytic function, α-enolase has been found to play an important role in several biological and pathophysiological processes. Particularly, α-enolase is considered to play important roles in tumorigenesis. This protein was found on the cell surface functioning as one of the plasminogen receptors which may play a role in tumor invasion (Redlitz et al., 1995, Eur J Biochem 227, 407-415). Up-regulation of α-enolase has been reported in several highly tumorigenic or metastatic cell lines (Chang et al., 2006, Clin Cancer Res 12, 5746-5754; Peebles et al., 2003, Carcinogenesis 24, 651-657; Satoshi Ito, 2007, Cancer Science 98, 499-505; Wu et al., 2002, Clin Exp Metastasis 19, 319-326; Zhang et al., 2000, J Surg Res 93, 108-119). α-enolase over-expression was correlated with tumorigenicity on several types of cancer which suggest its pathophysiologic role in cancer formation (Altenberg and Greulich, 2004, Genomics 84, 1014-1020). Furthermore, an autoantigen of α-enolase was identified in non-small cell lung cancer and its overexpression was highly correlated with poor survival outcomes (Chang et al., 2006, Clin Cancer Res 12, 5746-5754). In addition to its roles in cancer, α-enolase has been implicated in numerous diseases, including autoimmune disorders, ischemia and bacterial infection. (Antikainen et al., 2007, FEMS Immunol Med Microbiol 51, 526-534; Bogdanos et al., 2004, J Autoimmune Dis 1, 4; Gitlits et al., 2001, J Investig Med 49, 138-145; Jiang et al., 1997, Cancer Res 57, 5328-5335; Kinloch et al., 2005, Arthritis Res Ther 7, R1421-1429; Saulot et al., 2002, Arthritis Rheum 46, 1196-1201).
Therefore, α-enolase is a potential target for therapeutics of treating or preventing cancer development or for detection of cancer. There remains a need for detecting, treating, preventing, and reversing the development of cancers.